Background
Children with childhood trauma such as abuse, neglect, and loss of young parents are more likely to suffer from depression in adulthood [
1‐
6]. Cognitive vulnerability theory suggests that childhood trauma can lead to adverse cognitive schema, which is the basis of negative automatic thinking in depression [
1,
7]. Biological vulnerability theory suggests that childhood trauma increases vulnerability to depression through the interaction of genetics and one’s environment [
8]. Childhood trauma increases hypothalamic-pituitary-adrenal (HPA) axis activity, potentially mediating environmental risk for developing depression [
9]. The current literature indicates HPA axis hyperactivity in patients with depression, and this HPA axis hyperactivity is thought to be the outcome of childhood trauma and a predisposing factor to depression rather than the outcome of depression [
1]. However, HPA axis functioning hypoactivity has also been found in patients with depression [
10]. For example, one study reported that the cortisol awakening response was decreased after an early loss experience [
11]. However, another study found that parental loss was associated with increased cortisol awakening responses [
12].
Childhood neglect has the highest prevalence among types of childhood trauma in the United States [
13,
14]; however, studies on childhood neglect have found inconsistent results regarding the impact of childhood neglect on cortisol levels and HPA axis functioning [
12]. A study using the dexamethasone/corticotropin-releasing hormone test to measure HPA axis functioning found no significant differences in HPA axis functioning between depressed patients with high levels of childhood emotional neglect and healthy controls, but found significantly increased HPA axis functioning in depressed patients with low levels of childhood emotional neglect [
15]. Possible explanations for this finding may be that childhood neglect did not change the activity of the glucocorticoid receptors (GR), or that increased GR activity was offset by the hypoactivity caused by genetic factors. Another study found that cortisol levels were significantly different between depressed patients with and without childhood emotional neglect, but there was no significant difference among different types of childhood trauma classified by the Childhood Trauma Questionnaire (CTQ) subscale scores [
16]. The authors of that study proposed that emotional neglect was one of the most common types of childhood trauma, and that the lasting effect of chronic psychological stress on the HPA axis resulted in neurobiological changes [
17]. In addition, Beck suggested that childhood adversities might distort cognition about oneself and the world, and that depressed patients with childhood neglect often show dysfunctional attitudes, or a somewhat distorted cognitive schema [
18]. Some studies have suggested that a dysfunctional attitude is related to severity of depression, while others have proposed that it is a trait resulting from childhood trauma, and is not related to severity of depression [
19,
20]. At present, the relationships among childhood neglect, HPA axis functioning and dysfunctional attitude remain obscure. Therefore, in this study, we attempted to explore the impact of childhood neglect on HPA axis functioning, dysfunctional attitude and the severity of depression.
Discussion
Previous studies have suggested that childhood neglect could be a predictor of psychopathology, monoamine system dysfunction, and increased cerebrospinal fluid corticotropin-releasing hormone levels in adulthood, when compared with other forms of childhood trauma [
16,
35,
36]. In our study we focused predominantly on the impact of childhood neglect on HPA axis functioning, and Dysfunctional Attitude Scale (DAS) scores. Analysis of variance showed that there were significant differences in HPA axis functioning, DAS scores and Social Support Rating Scale (SSRS) scores among the four groups: depressed patients with childhood neglect, depressed patients without childhood neglect, healthy controls with childhood neglect and healthy controls without childhood neglect. Post hoc testing showed that HPA axis function activity was significantly higher in depressed patients with childhood neglect than in depressed patients without childhood neglect. This finding is consistent with previous studies and suggests that childhood neglect is related to hyperactivity of the HPA axis functioning. Animal experiments have demonstrated that when newborn rats and non-human mammals were separated from their mothers for a period of time, HPA axis activity increased and continued to increase into adulthood [
6]. Clinical studies have shown that HPA axis activity increased in men with childhood trauma [
9] and that women who suffered from childhood trauma showed adrenocorticotropic hormone hyperactivity and increased heart rates as adults after performing the Trier Social Stress Test, even if they did not suffer from depression in adulthood [
37]. In addition, we found that HPA axis activity was higher in the healthy control group with childhood neglect than in depressed patients without childhood neglect. This finding suggests that HPA axis activity was not always higher in the depressed patients than in healthy controls, and that childhood neglect might play an important role in the hyperactivity of the HPA axis functioning [
9,
37].
The DAS is a 40-item questionnaire designed to measure cognitive vulnerability for depression. Studies have reported that DAS scores were positively related to the Hamilton Rating Scale for Depression (HAMD) scores [
32], while others have thought that dysfunctional attitude was not state-dependent or symptom-dependent, but a trait associated with childhood trauma [
18,
38,
39]. Our results showed that DAS scores were not related to HAMD scores, but were positively related to childhood neglect scores. This supports the hypothesis that dysfunctional attitude is a trait resulting from childhood neglect. In our study we found that DAS scores were lowest in the healthy control group without childhood neglect and highest in depressed patients with childhood neglect. This finding provides further support for the hypothesis that childhood neglect plays an important role in the formation of dysfunctional attitude. Beck suggested that adversities that occur in childhood might distort cognition about oneself and the world, and that dysfunctional attitudes might underlie the negative automatic thoughts of depression [
19,
20].
Our results demonstrated that HPA axis functioning was related to childhood neglect but not to the severity of depression, which is consistent with findings from previous studies. Over the last 40 years, several studies have proposed that HPA axis hyperactivity is not a biological outcome of depression, but a predisposing factor that often results from childhood trauma [
40,
41]. Therefore, childhood neglect has been related to HPA axis functioning and HPA axis hyperactivity might be one of the risk factors for depression.
In addition, we did not find a correlation between childhood neglect and HAMD scores, but we found that SSRS scores were negatively related to HAMD scores. This might suggest that social support was helpful in alleviating the symptoms of depression. In our study, we found that the healthy control groups had higher SSRS scores than the depressed groups, which implies that social support might prevent depression.
Limitations: Our sample was relatively small. We used saliva cortisol awakening response as an index of HPA axis functioning, selecting only two time points (0 min, 30 min after awakening) on 2 consecutive days to collect the saliva sample. Though one study has reported this method to be sensitive and reliable [
42], further research should duplicate the results of the current study in a larger sample and with an optimized method of sampling over five time points (0 min, 15 min, 30 min, 45 min, 60 min after awakening) for cortisol collection. There are several potential unmeasured confounders known to be associated with cortisol collection, for example, compliance and sleep quality. In addition, the CTQ was used to measure childhood trauma; the self-report nature of this measure may have caused recall bias. We tried to overcome this problem by obtaining information about the subjects’ early life experiences from their first relatives. Finally, we suggest that more advanced statistical methods and a more powerful p-value correction should be performed in future research of this topic.
Acknowledgements
This study was supported by a grant from the National Natural Science Foundation of China (C090104 to Yuping Ning); the Medical Research Foundation of Guangdong, China (A2012523 to Hongjun Peng); the Science and Technology Program of Guangzhou, China (2010Y1-C631 to Yuping Ning and 2013 J4100096 to Hongjun Peng); the National Clinical Key Special Program (201201003 to Hongjun Peng).
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
Authors HP and YN designed the study and developed the protocols. YN and JL are tutors of HP. Authors HP, YL, JL, YG, and HW carried out literature searches and analyses. Authors YY, YD, JH and HP performed statistical analyses and prepared the first draft of the manuscript. All authors read and approved the final manuscript.